MULTIPHOTON MICROSCOPE REPLACEMENT FOR USC SHARED RESOURCE This proposal is submitted to purchase a new, high-end Leica SP8 AOBS multiphoton microscope with 1300nm IR laser for the Multi-Photon Microscopy Core at the Keck School of Medicine at USC. The new microscope will replace an old, non-operational model which is beyond repair and no longer serviced by the manufacturer. The new microscope will be a unique system dedicated to provide ultra-sensitive, deep tissue imaging of intact living organs in vivo in small animals with high spatial and temporal resolution that other intravital imaging modalities cannot achieve. The new core microscope is critically needed by a large research base of 14 NIH-funded investigators from four USC schools/campuses including the Keck School of Medicine, School of Pharmacy, Davis School of Gerontology, and the Herman Ostrow School of Dentistry. The proposed equipment will be used by these core investigators from seven major user groups/themes, including kidney, liver, stem cells, lung & lacrimal gland, brain, cancer, and dental imaging. The new microscope will make a substantial difference in USC's research activities and fulfill an unmet need for deep tissue intravital quantitative imaging for the study of organ functions in vivo in health and disease. The Zilkha Neurogenetic Institute, which is the academic unit housing this core is fully committed to the ongoing maintenance and operation of this new multiphoton microscope. The USC Multi-Photon Microscopy Core is an integral part of the Center of Excellence in Cell & Tissue Imaging, and the new microscope purchase will meet a strategic need expressed in the USC Plan for Science and Technology Facilities by providing instrumentation and collaborative expertise for biomedical and engineering research aimed at improving human health. Therefore, the USC Core Instrumentation Fund is providing significant cost-share ($200,000) toward the acquisition of this new microscope. Research supported by this core and new instrumentation will lead to our better understanding of the miracle of the brain, the normal functioning of the body's organs, the discovery of disease mechanisms and biomarkers, testing novel pharmaceuticals and biomedical devices, and the application of stem cells and regenerative medicine to cure degenerative disorders, and will help to keep USC at the leading edge of biomedical research.